Extensive Stage Small Cell Lung CarcinomaPhase 1/2NCT01737502
Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer
A Phase 1/2 study testing Auranofin, Sirolimus and Laboratory Biomarker Analysis in people with Extensive Stage Small Cell Lung Carcinoma and Lung Adenocarcinoma, run by Mayo Clinic at 2 sites in United States.
Trial summary
This phase I/II trial studies the side effects and best dose of auranofin when given together with sirolimus and to see how well it works in treating patients with lung cancer that has spread or other places in the body and cannot be cured or controlled by treatment or has come back after a period of time during which… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extensive Stage Small Cell Lung Carcinoma, Lung Adenocarcinoma, Recurrent Non-Small Cell Lung Carcinoma
- What is being tested?
- Auranofin, Sirolimus and Laboratory Biomarker Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 2 sitesUnited States
- Study dates
- 14 May 2014to 24 Apr 2023
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologic or cytologic confirmation of lung cancer (squamous, ras-mutated adenocarcinoma or small cell lung cancer)
- Patients must have received at least one course of chemotherapy consisting of a platinum doublet and must have no acceptable standard treatment options
- Prior radiation therapy is permitted as long as:
- Recovered from the toxic effects of radiation treatment before study entry, except for alopecia
- Absolute neutrophil count (ANC) >= 1500 uL
- Platelets (PLT) >= 100,000 uL
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- Hemoglobin (Hgb) >= 9 g/dL
- Total bilirubin =< 1.5 x upper limit of normal (ULN) or direct bilirubin =< ULN
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN or SGOT (AST) and SGPT (ALT) =< 5 x ULN is acceptable if liver has tumor involvement
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2
- Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- Ability to provide informed consent
- Life expectancy >= 12 weeks
- Willing to return to Mayo Clinic enrolling institution for follow-up
- Willing to provide tissue samples for correlative research purposes
Who cannot join
- Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- Symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases or seizure disorder; NOTE: patients with treated CNS metastases without evidence of progression and without uncontrolled symptoms or need for steroids may enroll
- Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded
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- Unwilling or unable to, comply with the protocol
- Any of the following prior therapies:
- Radiation to >= 25% of bone marrow
- Major surgery (i.e., laparotomy), open biopsy, or significant traumatic injury =< 4 weeks prior to registration; minor surgery =< 2 weeks prior to registration; insertion of a vascular access device is not considered major or minor surgery in this regard
- Any of the following concurrent severe and/or uncontrolled medical conditions:
- Hypertension, labile hypertension, or history of poor compliance with antihypertensive medication
- Angina pectoris
- History of congestive heart failure =< 3 months, unless ejection fraction > 40%
- Myocardial infarction =< 6 months prior to registration
- Cardiac arrhythmia
- Poorly controlled diabetes
- Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
- Active or recent history of hemoptysis; if hemoptysis has resolved with measures such as palliative radiation therapy (e.g. 3000 cGy over 10 fractions), arteriographic embolization or endobronchial interventions (e.g. photodynamic therapy, brachytherapy), etc. for > 14 days, patients may be considered for participation in this study
- >= Grade 2 hypertriglyceridemia
- >= Grade 2 hypercholesterolemia
- Any illness that in the opinion of the investigator would compromise the ability of the patient to participate safely in the clinical trial
- Use of St. John's Wort because of its effects on hepatic drug metabolism
- Other active malignancy: EXCEPTIONS: Non-melanoma skin cancer, localized prostate cancer, or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, patient must not be receiving other cytotoxic or molecularly targeted therapeutics treatment for their cancer; patients receiving certain hormonal manipulations as part of their treatment may be allowed to continue at the discretion of the Principal Investigator (PI) (e.g. luteinizing hormone-releasing hormone [LHRH] analogs for prostate cancer)
- Unable to discontinue use of potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors/inducers
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mayo Clinic
Jacksonville, Florida, 32224
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
About this study
Official title: A Phase I-II Trial of Combined PKCι and mTOR Inhibition for Patients With Advanced or Recurrent Lung Cancer (NSCLC and SCLC) Without Standard Treatment Options
This phase I/II trial studies the side effects and best dose of auranofin when given together with sirolimus and to see how well it works in treating patients with lung cancer that has spread or other places in the body and cannot be cured or controlled by treatment or has come back after a period of time during which the cancer could not be detected. Auranofin and sirolimus may stop or slow the growth of lung cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To establish the maximum tolerated dose of auranofin plus sirolimus after at least one line of platinum based chemotherapy for lung cancer (squamous, ras-mutated adenocarcinoma, or small cell lung cancer) patients with no acceptable standard treatment options. (Phase I) II. To assess the progression-free survival at four months of patients treated with auranofin after at least one line of platinum based chemotherapy for lung cancer (squamous, ras-mutated adenocarcinoma, or small cell lung cancer) patients with no acceptable standard treatment options. (Phase II)
SECONDARY OBJECTIVES:
- To assess the overall survival in this population in comparison to recent historical controls.
II. To determine the adverse events (AE) profile and safety of the regimen. III. To determine the overall response rate, per Response Evaluation Criteria In Solid Tumors (RECIST) criteria, and duration of tumor response in those patients with measurable disease.
TERTIARY OBJECTIVES:
- To assess the relationship between molecular correlates and progression-free survival (PFS), overall survival (OS), response and adverse events.
OUTLINE: This is a phase I, dose-escalation study of auranofin followed by a phase II study.
Patients receive auranofin orally (PO) on days 1-28 and sirolimus PO on days 1-28 (days 8-28 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-6 months for 5 years.
- Conditions
- Extensive Stage Small Cell Lung Carcinoma, Lung Adenocarcinoma, Recurrent Non-Small Cell Lung Carcinoma, Recurrent Small Cell Lung Carcinoma, Squamous Cell Lung Carcinoma, Stage IIIA Non-Small Cell Lung Cancer
- Being tested
- Auranofin, Sirolimus, Laboratory Biomarker Analysis, Pharmacological Study
- Medical subject headings
- Adenocarcinoma of Lung, Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AuranofinDrug
Also called Ridaura
Given PO
SirolimusDrug
Also called AY 22989, RAPA, SILA 9268A, WY-090217
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (auranofin and sirolimus) | Experimental | Patients receive auranofin PO on days 1-28 and sirolimus PO on days 1-28 (days 8-28 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Auranofin; Drug: Sirolimus; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Phase 1 Patients Experiencing a DLT
The number and severity of all adverse events (overall and by dose level) will be tabulated and summarized. A DLT is defined as an adverse event during the first cycle of, at least possibly related to study treatment, and one of the following: Grade 4 Neutropenia, Grade 4 Thrombocytopenia, ≥Grade 3 Anaphylaxis, ≥Grade 3 Proteinuria, ≥Grade 3 Hematuria, ≥Grade 3 Rash acneiform, ≥Grade 3 Diarrhea, ≥Grade 3 Mucositis oral
Measured: 28 days
Number Phase 1 Patients Experiencing a Grade 3+ AE
Number and severity of all adverse events (overall and by dose level) will be tabulated and summarized.
Measured: Up to 5 years
Progression-free Survival Rate
A patient is considered to be a 4-month progression-free survivor, or success, if the patient is 4 months from registration without a documentation of disease progression. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated using the properties of the binomial distribution. Additionally, an estimate and confidence interval for the 4-month progression-free survival rate incorporating censoring may be computed using the method of Kaplan-Meier.
Measured: 4 months
Secondary outcomes (4)
Overall Survival Time
Overall Survival (OS) is defined as the length of time from study enrollment until death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Measured: up to 5 years
Progression-free Survival Time
Progression-free survival is defined as the time from study enrollment until disease progression or death from any cause. The distribution of progression-free survival time will be estimated using the method of Kaplan-Meier.
Measured: up to 5 years
Number of Patients Achieving a Complete Response (CR) or Partial Response (PR) Noted as the Objective Status
The overall response rate will be estimated in the subset of patients with measurable disease by the number of responses in evaluable patients with measurable disease divided by the total number of evaluable patients with measurable disease.
Measured: Up to 5 years
Duration of Response
Defined for all evaluable patients with measurable disease who have achieved a response as the date at which the patient's earliest best objective status is first noted to be a CR or PR to the earliest date progression is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2012 (estimated)
- Study start14 May 2014
- Primary completion24 Apr 2023
- Study completion24 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Extensive Stage Small Cell Lung CarcinomaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Yanyan Lou, M.D., Ph.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01737502
- Sponsor's protocol ID
- MC1125
- Other IDs
- NCI-2012-00518, 11-001987, R21CA153000
- Status last verified
- Mar 2024
- First submitted
- 27 Nov 2012
- Last updated
- 5 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Jatoi A, Foster NR, Wahner Hendrickson A, Block MS, Weroha SJ, Asmus EJ, Murray NR, Fields AP. A Phase 2 Trial of Protein Kinase C Iota Inhibition With the Combination of Auranofin and Sirolimus in Patients With Recurrent Ovarian Cancer. Am J Clin Oncol. 2026 May 1;49(5):238-242. doi: 10.1097/COC.0000000000001263. Epub 2025 Oct 20.
PubMed 41114938Rousselle B, Massot A, Privat M, Dondaine L, Trommenschlager A, Bouyer F, Bayardon J, Ghiringhelli F, Bettaieb A, Goze C, Paul C, Malacea-Kabbara R, Bodio E. Conception and Evaluation of Fluorescent Phosphine-Gold Complexes: From Synthesis to in vivo Investigations. ChemMedChem. 2022 Jun 3;17(11):e202100773. doi: 10.1002/cmdc.202100773. Epub 2022 Mar 29.
PubMed 35254001